Methods of treating parkinson's disease using viral vectors
View Patent ↗Methods of delivering viral vectors, particularly recombinant AAV virions, to the CNS are provided. Also provided are methods of treating Parkinson's Disease.
1. A method of delivering recombinant adeno-associated virus virions to the brain of a primate, said method comprising:
(a) providing a composition comprising at least 2.5x10 9 recombinant adeno-associated virus virions, wherein said recombinant adeno-associated virus virions comprise a recombinant nucleotide sequence of interest that encodes a protein; and
(b) administering said composition to said brain using a non-manual pump such that distribution of said recombinant adeno-associated virus virions over an area greater than 5 mm 2 is achieved.
2. The method of claim 1 , wherein the composition provided in (a) comprises at least 2.5x10 10 recombinant adeno-associated virus virions.
3. The method of claim 1 , wherein said protein is aromatic amino acid decarboxylase (AADC).
4. The method of claim 1 , wherein said pump is an infusion pump or an osmotic pump.
5. The method of claim 1 , wherein said composition is administered to striatum of the brain.
6. The method of claim 1 , wherein said composition is administered under a pressure gradient.
7. The method of claim 1 , wherein said method further comprising administering oral L-dopa to said primate.
8. The method of claim 1 , wherein said primate suffers from a central nervous system (CNS) disorder.
9. The method of claim 8 , wherein said CNS disorder is Parkinson's disease.
10. A method of delivering recombinant adeno-associated virus virions to the brain of a primate, said method comprising:
(a) providing a composition comprising at least 2.5x10 10 recombinant adeno-associated virus virions, wherein said recombinant adeno-associated virus virions comprise a recombinant nucleotide sequence of interest that encodes a protein; and
(b) administering said composition to said brain using a non-manual pump such that distribution of said recombinant adeno-associated virus virions over a volume of at least 250mm 3 is achieved.
11. The method of claim 10 , wherein said protein is aromatic amino acid decarboxylase (AADC).
12. The method of claim 10 , wherein said pump is an infusion pump or an osmotic pump.
13. The method of claim 10 , wherein said composition is administered to striatum of the brain.
14. The method of claim 10 , wherein said composition is administered under a pressure gradient.
15. The method of claim 10 , wherein said method further comprising administering oral L-dopa to said primate.
16. The method of claim 10 , wherein said primate suffers from a central nervous system (CNS) disorder.
17. The method of claim 16 wherein said CNS disorder is Parkinson's disease.
18. A method of delivering recombinant adeno-associated virus virions over an area of the central nervous system (CNS) of a primate, said method comprising:
(a) providing a composition comprising at least 2.5x10 10 recombinant adeno-associated virus virions, wherein said recombinant virions comprise a recombinant nucleotide sequence of interest that encodes a protein; and
(b) administering said composition to the CNS of the primate such that distribution of said recombinant virions over an area greater than 5 mm 2 or over a volume of at least 250 mm 3 is achieved, wherein said composition is administered by convention-enhanced delivery using a non-manual pump.
19. The method of claim 18 , wherein said protein is aromatic amino acid decarboxylase (AADC).
20. The method of claim 18 , wherein said pump is an infusion pump or an osmotic pump.
21. The method of claim 18 , wherein said composition is administered to striatum of the brain.
22. The method of claim 18 , wherein said composition is administered under a pressure gradient.
23. The method of claim 18 , wherein said method further comprising administering oral L-dopa to said primate.
24. The method of claim 18 , wherein said CNS disorder is Parkinson's disease.
25. A method of delivering recombinant adeno-associated virus virions to the brain of a primate suffering from Parkinson's disease, said method comprising:
(a) providing a composition comprising at least 2.5x10 10 recombinant adeno-associated virus virions, wherein said recombinant adeno-associated virus virions encode aromatic amino acid decarboxylase (AADC);
(b) orally administering L-dopa to said primate; and
(c) administering said composition to striatum of said primate using an infusion pump such that distribution of said recombinant adeno-associated virus virions over an area greater than 5 mm 2 or over a volume of at least 250 mm 3 is achieved.
26. The method of claim 25 , wherein said composition is administered under a pressure gradient.
27. A method of delivering recombinant adeno-associated virus virions to the striatum of the brain of a primate, said method comprising:
(a) providing a composition comprising at least 2.5x10 10 recombinant adeno-associated virus virions, wherein said recombinant adeno-associated virus virions comprise a recombinant nucleotide sequence of interest that encodes a protein; and
(b) administering said composition to said brain using an infusion pump or an osmotic pump such that distribution of said recombinant adeno-associated virus virions over an area greater than 5 mm 2 or over a volume of at least 250 mm 3 is achieved.
28. The method of claim 27 , wherein said composition is administered under a pressure gradient.